Retinal Pigment Measurement Could Signal Early Alzheimer’s

Results to be showcased internationally in the Journal of Alzheimer’s Disease.

Researchers at the Macular Pigment Research Group (MPRG) at Waterford Institute of Technology (WIT), supported by European Research Council (ERC) funding, have published findings that strengthen the case for using macular pigment as a non-invasive biomarker of cognitive health. The study links macular pigment optical density (MP) in the eye to multiple measures of cognitive performance and contrasts those associations with blood levels of the macular carotenoids lutein and zeaxanthin.

The clinical trial in Waterford involved a multidisciplinary team of ten researchers and healthcare professionals. The investigators enrolled two distinct participant groups: people without retinal disease but with low macular pigment (Group 1), and people diagnosed with early age-related macular degeneration (AMD) (Group 2). The research aimed to determine how MP measured in the eye and serum concentrations of lutein (L) and zeaxanthin (Z) relate to cognitive function across these groups.

All participants underwent comprehensive testing in the analytical and vision laboratories at Carriganore House on WIT’s West Campus, where the MPRG is based. Macular pigment was assessed by customized heterochromatic flicker photometry and dual-wavelength autofluorescence. Serum lutein and zeaxanthin concentrations were quantified using high-performance liquid chromatography (HPLC). Cognitive performance was evaluated using a validated battery of neuropsychological tests covering domains such as verbal memory, semantic fluency, and recognition memory.

The study found consistent, statistically significant relationships between macular pigment levels and several measures of cognitive performance in both participant groups (correlation coefficients ranged from r = –0.273 to r = 0.261, p ≤ 0.05). In contrast, serum lutein and zeaxanthin showed significant correlations with cognitive performance on only a limited number of tests. Specifically, in the AMD group, both serum lutein and zeaxanthin correlated with semantic (animal) fluency (r = 0.187 and r = 0.197, respectively, p ≤ 0.05), and serum lutein also correlated with the Verbal Recognition Memory learning slope (r = 0.200, p = 0.031).

Importantly, when researchers adjusted for potential confounding factors including age, sex, diet, and education, the associations between macular pigment and cognitive measures remained statistically significant. The associations between serum lutein and zeaxanthin and cognition, however, did not remain significant after these controls. These findings suggest macular pigment optical density may be a more robust and clinically useful marker of cognitive function than circulating carotenoid levels alone.

Professor John Nolan, Principal Investigator at the MPRG and an ERC-funded fellow, commented on the implications: “With Alzheimer’s disease and other forms of cognitive decline on the rise, identifying accessible biomarkers that reflect brain health is crucial. Our results indicate that measuring macular pigment could help detect individuals at higher risk of cognitive impairment earlier than current approaches.” He emphasized the value of publishing the study in the Journal of Alzheimer’s Disease to reach a global clinical and research audience.

This shows a blue eye.
After controlling for age, gender, diet, and education, correlations between macular pigment and cognitive function remained statistically significant, whereas correlations between serum lutein and zeaxanthin and cognitive function did not. Image for illustrative purposes only.

The research has been made available online ahead of the journal’s September issue, offering clinicians and scientists early access to the data and interpretations. Dr. George Perry, Editor-in-Chief of the Journal of Alzheimer’s Disease, noted that the study’s unexpected and novel results provide both conceptual insight and immediate therapeutic potential for patient care and risk detection.

About this Alzheimer’s disease research

Source: IOS Press
Image Credit: The image is in the public domain
Original Research: Abstract for “Cognitive Function and Its Relationship with Macular Pigment Optical Density and Serum Concentrations of its Constituent Carotenoids” by David Kelly, Robert F. Coen, Kwadwo Owusu Akuffo, Stephen Beatty, Jessica Dennison, Rachel Moran, Jim Stack, Alan N. Howard, Riona Mulcahy, and John M. Nolan. Published online August 6, 2015; doi:10.3233/JAD-150199.


Abstract

Cognitive Function and Its Relationship with Macular Pigment Optical Density and Serum Concentrations of its Constituent Carotenoids

Macular pigment (MP) reflects retinal concentrations of the carotenoids lutein (L) and zeaxanthin (Z), and prior research has linked higher MP to better cognitive performance across age groups. This study assessed MP, serum L and Z, and cognitive function in two cohorts: participants without retinal disease but with low MP (MP at 0.25 degrees eccentricity < 0.5 optical density units; Group 1, n = 105) and participants with age-related macular degeneration (Group 2, n = 121). MP was measured by customized heterochromatic flicker photometry and dual-wavelength autofluorescence; serum L and Z were quantified by HPLC; cognitive function was measured with a validated battery of tests.

Results showed multiple significant correlations between MP and cognitive outcomes in both groups (r = –0.273 to 0.261, p ≤ 0.05). In the AMD group, serum L and Z correlated with semantic (animal) fluency (r = 0.187, p ≤ 0.05 and r = 0.197, p ≤ 0.05, respectively), and serum L correlated with the Verbal Recognition Memory learning slope (r = 0.200, p = 0.031). After controlling for age, sex, diet, and education, most correlations involving MP remained significant, while correlations involving serum L and Z did not.

Conclusion: Macular pigment optical density shows promise as a non-invasive clinical biomarker of cognitive health and appears to outperform serum lutein and zeaxanthin concentrations in this role.

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